6-Hydroxydopamine is a neurotoxin which, in our Branch, has recently been shown to be produced endogenously, in very small amounts in normal rat brains. This neurotoxin is probably produced as a by-product of dopamine degradation. Since motor hyperexcitation is a frequent manifestation of psychotic states, the question has been raised as to whether physical hyperactivity may increase brain dopamine and consequently brain 6- hydroxydopamine, and thereby contribute to the brain dysfunction frequently seen in schizophrenia. In an attempt to answer this question, a rat model of physical stress by forced wheel running is being developed. The model would involve forced wheel running of Brown-Norway rats to the point of exhaustion. Recovery would be monitored by open field behaviors. Biochemical studies involving dopamine, its metabolites (including 6- hydroxydopamine), and other neurochemicals would help delineate the role of physical hyperactivity and concomitant stress on brain function. The wheel running apparatus has been constructed and the protocol has been approved by the ACUC.